The Murine SCP3 Gene Is Required for Synaptonemal Complex Assembly, Chromosome Synapsis, and Male Fertility

Abstract

During meiosis, the homologous chromosomes pair and recombine. An evolutionarily conserved protein structure, the synaptonemal complex (SC), is located along the paired meiotic chromosomes. We have studied the function of a structural component in the axial/lateral element of the SC, the synaptonemal complex protein 3 (SCP3). A null mutation in the SCP3 gene was generated, and we noted that homozygous mutant males were sterile due to massive apoptotic cell death during meiotic prophase. The SCP3-deficient male mice failed to form axial/lateral elements and SCs, and the chromosomes in the mutant spermatocytes did not synapse. While the absence of SCP3 affected the nuclear distribution of DNA repair and recombination proteins (Rad51 and RPA), as well as synaptonemal complex protein 1 (SCP1), a residual chromatin organization remained in the mutant meiotic cells.

Evolutionary history of the mammalian synaptonemal complex

“…In mouse meiocytes, SYCP3 is essential for AE assembly. The AE formation is abolished in the absence of SYCP3 (Liebe et al 2004) and the second axial component SYCP2 cannot be recruited to the chromosomes anymore (Yuan et al 2000). Expression of a C-terminally truncated SYCP2 leads to a failure of AE formation in mouse spermatocytes as well (Yang et al 2006).…”

Structural components of the synaptonemal complex, SYCP1 and SYCP3, in the medaka fish Oryzias latipes

“…In Sycp3-deficient mice, meiosis is stopped at the zygotene stage, and spermatogenic cells at later stages, including metaphase I, are not present in the testis because the spermatogenesis is arrested at the checkpoint that monitors several key events, including failure to form the SC [11]. Therefore, we cannot examine the role of SYCP3 at metaphase I by using Sycp3-deficient mice.…”

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

“…Of interest, mutations abrogating Rad51, Dmc1 and other repair protein encoding genes results in a similar phenotype to that of Spo11 mutant mice (Pittman et al, 1998;Yoshida et al, 1998;Sharan et al, 2004). In addition, mutations in components of SC and cohesion core formation lead to a similar phenotype (Bannister et al, 2004;Kolas et al, 2004;Yuan et al, 2000). Most mutations in meiotic genes appear to cause a similar phenotype in which spermatocytes fail to progress past the zygotene stages (reviewed in Morelli and Cohen, 2005).…”